THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OR AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEND ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE ABSTRACT BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. DESCRIPTION: Kaposi's sarcoma (KS) is the most common malignancy associated with AIDS. Many lines of evidence support the involvement of cytokines in the induction and maintenance of the proliferative state of the tumor cells, and a regulatory role of HIV-1 has been proposed. Recent studies have suggested an etiologic role for a newly discovered human herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV) in the pathogenesis of KS. Retroperitoneal fibromatosis (RF) is a fibroproliferative disease of macaques with many of the morphological and histological similarities to KS, including an associated retrovirus, simian retrovirus-1 (SRV-2). The investigators have discovered herpes- like sequences corresponding to DNA polymerase and glycoprotein B genes in RF malignancies. These sequences identify a previously unknown herpesvirus in RF which appears to be the simian counterpart of KSHV. These findings support the relevance of RF in macaques as a model system for KS in humans and suggest a role for KSHV-like herpesviruses in the etiology of fibroproliferative diseases such as KS and RF. The goals of this project are to determine the interactions of this class of herpesvirus with retroviruses and endogenous cellular factors in the induction and progression of these malignancies. The specific aims of the application are to: 1) obtain evidence that the DNA pol and glyB fragments identified in RF and KS lesions are derived from the genomes of related herpesviruses; 2) identify latency- and transformation- associated genes in RFHV and KSHV using consensus PCR assays; 3) identify cell and tissue types containing RFHV genome and establish cell cultures from them in vitro; 4) identify RFHV and KSHV genes which are expressed in RF and KS lesions in vivo and in cell cultures which contain viral genomes in vitro; 5) investigate the role of RFHV and KSHV in the induction of cytokine expression in RF and KS lesions in vivo and in infected cell cultures. Such studies could resolve many important questions concerning the etiology of KS, its mode of transmission, and the importance of viruses and viral regulation of cellular factors in the pathogenesis of KS.